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dc.contributor.authorNarverud, Ingunn
dc.contributor.authorChristensen, Jacob J.
dc.contributor.authorBakke, Siril Skaret
dc.contributor.authorUlven, Stine Marie
dc.contributor.authorRundblad, Amanda
dc.contributor.authorAukrust, Pål
dc.contributor.authorEspevik, Terje
dc.contributor.authorBogsrud, Martin Prøven
dc.contributor.authorRetterstøl, Kjetil
dc.contributor.authorUeland, Thor
dc.contributor.authorHalvorsen, Bente
dc.contributor.authorHolven, Kirsten Bjørklund
dc.date.accessioned2020-03-09T07:22:10Z
dc.date.available2020-03-09T07:22:10Z
dc.date.issued2019-10-21
dc.description.abstract<i>Background</i> - Innate and adaptive immune responses are pivotal in atherosclerosis, but their association with early‐stage atherosclerosis in humans is incompletely understood. In this regard, untreated children with familial hypercholesterolaemia may serve as a human model to investigate the effect of elevated low‐density lipoprotein (LDL)‐cholesterol.<p><p> <i>Objectives</i> - We aimed to study the immunological and inflammatory pathways involved in early atherosclerosis by examining mRNA molecules in peripheral blood mononuclear cells (PBMCs) from children with FH.<p><p> <i>Methods</i> - We analysed the level of 587 immune‐related mRNA molecules using state‐of‐the‐art Nanostring technology in PBMCs from children with (<i>n</i> = 30) and without (<i>n</i> = 21) FH, and from FH children before and after statin therapy (<i>n</i> = 10).<p><p> <i>Results</i> - 176 genes (30%) were differentially expressed between the FH and healthy children at <i>P</i> < 0.05. Compared to healthy children, the dysregulated pathways in FH children included the following: T cells (18/19); B cells (5/6); tumour necrosis factor super family (TNFSF) (6/8); cell growth, proliferation and differentiation (5/7); interleukins (5/9); toll‐like receptors (2/5); apoptosis (3/7) and antigen presentation (1/7), where the ratio denotes higher expressed genes to total number of genes. Statin therapy reversed expression of thirteen of these mRNAs in FH children.<p><p> <i>Conclusion</i> - FH children display higher PBMC expression of immune‐related genes mapped to several pathways, including T and B cells, and TNFSF than healthy children. Our results suggest that LDL‐C plays an important role in modulating expression of different immune‐related genes, and novel data on the involvement of these pathways in the early atherosclerosis may represent future therapeutic targets for prevention of atherosclerotic progression.en_US
dc.identifier.citationNarverud I, Christensen JJ, Bakke SS, Ulven S, Rundblad A, Aukrust P, Espevik T, Bogsrud MP, Retterstøl K, Ueland T, Halvorsen BE, Holven KB. Profiling of immune-related gene expression in children with familial hypercholesterolaemia. Journal of Internal Medicine. 2019:1-12en_US
dc.identifier.cristinIDFRIDAID 1756956
dc.identifier.doi10.1111/joim.13001
dc.identifier.issn0954-6820
dc.identifier.issn1365-2796
dc.identifier.urihttps://hdl.handle.net/10037/17658
dc.language.isoengen_US
dc.publisherWileyen_US
dc.relation.journalJournal of Internal Medicine
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/SFF/223255/Norway/Centre of Molecular Inflammation Research/CEMIR/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2019 The Author(s)en_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.titleProfiling of immune-related gene expression in children with familial hypercholesterolaemiaen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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